tbuckley/cabot-search huggingface dataset:
PB1984: FACTORS ASSOCIATED WITH PROGRESSION-FREE SURVIVAL IN CHRONIC MYELOID LEUKEMIA PATIENTS ATTENDED AT FOSCAL IN THE PERIOD 2013-2020
Authors: Néstor Gamboa, Ángela María Peña, Luis Antonio Salazar, Gabriela Vesga-Jerez, Ana María Prada-Sepúlveda, María Luna-González, Miguel Ochoa, Claudia Lucía Sossa, Virgnia Abello
Journal: HemaSphere (2023)

Topic: 8. Chronic myeloid leukemia - Clinical Background: Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm characterized by the unregulated production of mature granulocytes and the BCR/ABL fusion gene presence. The age of presentation is between 45 to 55 years, however up to 30% of patients will be 60 years or over at diagnosis. It has been evidenced that the five-year survival rate is 80% greater with the development of Tyrosine Kinase Inhibitors (TKIs). Aims: The aim of this study was to determine factors associated with progression-free survival in chronic myeloid leukemia patients attended at FOSCAL in the 2013-2020. Methods: Secondary analysis of an anonymized database of CML patients attended at FOSCAL and included in RENEHOC (online platform). Univariate analysis was performed to characterize the population and bivariate for Kaplan-Meier survival and Hazard Ratio (HR) for the risk ratio. STATA V14 was used as a statistical package. Approval was given by the institutional ethics committee (06223/2022). Results: A total of 122 patients were attended at FOSCAL. The mean age was 56 years (SD 16) and 55% were women. Regarding to the risk assessment at diagnosis, 21.3% and 29.5% had a low score on Sokal and Hasford Index, respectively. During the first line of treatment, the most used drug was Imatinib (67.5%), followed by Dasatinib (20.5%) and Nilotinib (6.5%). Regarding optimal responses, 73.8% achieved hematological response, 62% cytogenetic response and 51% molecular response. Within the first line of treatment, 37.7% of patients had disease progression, in which 36.9% progressed to loss of hematologic response and 34.7% to loss of molecular response. Drug response loss was documented with Dasatinib (16%), Nilotinib (12.5%) and Imatinib (47.5%) with a statistically significant difference (p=0.03). It was observed that an age older than 65 years HR 0.77 (95%CI 0.18-3.31; p=0.72) promote PFS; while a high level on the Sokal and Hasford Index were against PFS HR 1.76 (95%CI 0.5-6.16; p=0.37) and HR 1.33 (95%CI 0.58-3.06; p=0.5) respectively; however, none of these results were statistically significant (Image 1). Summary/Conclusion: Even though data were not statistically significant, it was suggestive that age over 65 years and male gender represent greater progression-free survival, while a high score on the risk scales acts against this outcome.Keywords: Chronic myeloid leukemia, Survival
P1612: CALPROTECTIN LEVELS ARE ELEVATED IN CONGENITAL TTP AND IMMUNE TTP AT ADAMTS13 RELAPSE
Authors: Maryam Subhan, Bertina Dragunaite, Marie Scully, Rens de Groot
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: Calprotectin (also known as S100A8/A9) is a proinflammatory protein that is secreted by neutrophils. A previous study by Sui et al (2020) demonstrated calprotectin was elevated during acute immune TTP episodes, with higher levels associated with mortality; and postulated that it may also be involved in the pathogenesis of TTP by playing a role in thrombus formation. Aims: We sought to examine whether calprotectin levels were elevated in TTP patients in different clinical scenarios to determine if it could be used to predict relapse or was simply a marker of inflammation during acute episodes. Methods: A retrospective study was carried out in patients consented to the UK TTP registry where frozen, citrated plasma was thawed and levels were measured using a human S100A8/A9 DuoSet ELISA kit (R&D Systems, Minneapolis, MN), according to the manufacturer’s instructions. In total, 95 TTP patient episodes were tested, of which 40 were patients that had an ADAMTS13 relapse, 30 were congenital patients and 5 were immune TTPs in complete remission. The remaining episodes were acute: 12 immune TTP and 8 congenital TTP. The mean age of patients at the time of an episode was 42 years (range 0 – 83 years). 40 normal control citrated plasma samples were also tested. Results: In clinical remission, the median calprotectin level for ADAMTS13 relapse episodes was 0.76 µg/ml (range 0.02 – 2.31), which was similar to congenital patients at 0.72 µg/ml (0.03 – 14.45) but significantly higher than normal controls: 0.33 µg/ml (0.06 – 0.91). Interestingly, although only 5 TTP patients in complete remission were tested, their calprotectin level was also raised compared to normal controls at 0.6 µg/ml (0.33 – 1.22). Levels were considerably higher in acute episodes with 15.3 µg/ml (4.9 – 242) in congenital patients and 64.3 µg/ml (0.99-332) in immune TTP patients. Summary/Conclusion: Calprotectin is markedly elevated during both acute immune and congenital TTP episodes. During remission or prior to elective therapy, levels are much lower although not as low as normal controls. Our findings suggest that even in clinical remission, for both immune and congenital TTP patients alike, there seems to be some ongoing inflammatory activity. This may have long-term implications for patients and requires further study.Figure: Calprotectin levels in congenital TTP patients, ADAMTS13 relapses in clinical remission and normal controls. **** refers to a p-value <0.0001. Keywords: Thrombotic thrombocytopenic purpura (TTP), Thrombotic microangiopathy
P948: REAL-WORLD EVIDENCE OF BISPHOSPHONATES FOR MULTIPLE MYELOMA
Authors: Maria Nieves Lopez Muñoz, Gema Hernández, Rafael Alonso, Jose Maria Sanchez Pina, Clara Cuellar, Ana Jimenez Ubieto, Esther Parra, Alberto Blanco, Guillermo Ramos, Maria Calbacho, Rosa Ayala, Joaquin Martinez-Lopez
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Bisphosphonates are widely used in multiple myeloma; but only a randomized clinical have showed that zolendronic acid improved survival as well as reduce the number of bone events. We used data from TriNetx, a global federated health research platform that includes patients from Europe and US Aims: The objective of this study is analyze the impact of bisphosphonates treatment in a large cohort of patients with multiple myeloma. Methods: Comparator cohorts included 16,995 MM patients from US and EMEA Collaborative Networks, 6464 were treated with bisphosphonates. After propensity scoring matching by age, sex, and date of diagnosis we selected 5849 patients in each cohorts. Patients had symptomatic multiple myeloma (ICD-10-CM code C90.0) diagnosed between 2007 and 2022. Patients treated with bisphosphonates included: Pamidronate and Zolendromic acid. Kaplan‒Meier analysis was used to estimate survival probabilities, and between-group differences were tested using the log-rank test and hazard ratio. Results: Patients not treated with bisphosphonates had more bone event as fractures of sternum, spine, long bones, and pelvis (40% vs 18%). Also, patients treated with bisphosphonates had a significant longer overall survival (OS) (HR 1.35 (1.23-1.48, p<0.001). The probability of OS at 3y is 73% in the group treated with bisphosphonates versus those untreated, that have a probability of survival at 3y of 70%. (Figure 1). Summary/Conclusion: This large-scale study based on real-world data confirms the bisphosphonates prolong survival in MM. Figure 1. Overall Survival by cohorts: In purple patients treated with bisphosphonates, in green patients without bisphosphonates (p<0.001)Keywords: Bisphosphonate, Multiple myeloma, Survival, Bone disease
P1559: ASSOCIATION BETWEEN TNF-Α LEVELS AND FALCIPARUM MALARIA PANCYTOPENIA AMONG SUDANESE CHILDREN
Authors: Khalid Abdelsamea Mohamedahmed
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Falciparum malaria is the most leading causes of mortality and morbidity in the world especially in Africa infant and young children due to severe malaria and malaria anemia. Aims: The purpose of this study was to evaluate the association between TNF-α levels and falciparum malaria anemia in Sudanese children. Methods: A case control study was conducted on 200 Sudanese children (100 children with complicated falciparum malaria [mean age 8.6 ± 3.4 years, 61% male]; 100 children with uncomplicated falciparum malaria [mean age 8.8 ± 4.2 years, 45% male]). The Blood cells parameters were measured using Sysmex XP 300 N Automated Analyzer. Cytopenia define as presence of anemia or leukocytopenia or thrombocytopenia, bicytopenia define as presence of two of cytopenia, pancytopenia define as presence of all cytopenia. TNF-α levels was measured using Human TNF-α ELISA MAX™ Deluxe Sets –BioLegend, Inc. The data were analyzed using SPSS software (V 20.0). Results: The malaria cytopenia, bicytopenia and pancytopenia were determined in 79 (39.5%), 31 (16.5%) and 7 (3.5%) cases respectively; and 50 (50%), 27 (27%) and 7 (7%) cases respectively among severe malaria giving highly significant association between them (P value 0.010). The average of TNF-α levels in serum of the patients with malaria with cytopenia types was (211.04 ± 100.16 ng/L) higher than patients with malaria without cytopenia types (126.20 ± 54.71 ng/L) (P value 0.000). While, the average of TNF-α levels in serum of the malaria cytopenia, bicytopenia and pancytopenia cases were (161.92 ± 79.22, 205.46 ± 105.34 and 265.75 ± 115.91 ng/L respectively) giving statistically significant differences between TNF-α levels (P value 0.004) and significant positive correlation (P value 0.006, r = +0.286). Otherwise, Most malaria cytopenia, bicytopenia and pancytopenia cases had TNF-α levels more than 100 ng/L (80.6%, 96% and 100% respectively). 6 (85.7%) of Malaria pancytopenia cases had malaria hyperparasitemia. Summary/Conclusion: The study results showed that the TNF-α level is highly levels in pancytopenia and correlated with types of cytopenia, so the falciparum malaria cytopenia types diagnosis may help as prognostic tool to assess the disease severity and its management by identifying the patients at high risk for the disease. Title: ASSOCIATION BETWEEN TNF-Α LEVELS AND FALCIPARUM MALARIA PANCYTOPENIA AMONG SUDANESE CHILDREN Keywords: Pancytopenia, Malaria, Tumor necrosis factor (TNF)
Balancing Efficacy and Tolerability of First-Line Systemic Therapies for Advanced Hepatocellular Carcinoma: A Network Meta-Analysis
Authors: Ciro Celsa, Giuseppe Cabibbo, David James Pinato, Gabriele Di Maria, Marco Enea, Marco Vaccaro, Salvatore Battaglia, Giacomo Emanuele Maria Rizzo, Paolo Giuffrida, Carmelo Marco Giacchetto, Gabriele Rancatore, Maria Vittoria Grassini, Calogero Cammà
Journal: Liver Cancer (2023)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Atezolizumab + bevacizumab represent the current standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). However, direct comparison with other combination treatments including immune checkpoint inhibitors (ICI) + tyrosine kinase inhibitors (TKIs) are lacking. &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; This network meta-analysis (NMA) aims to indirectly compare the efficacy and the safety of first-line systemic therapies for unresectable advanced HCC. &lt;b&gt;&lt;i&gt;Method:&lt;/i&gt;&lt;/b&gt; A literature search of MEDLINE, Embase, and SCOPUS databases was conducted up to October 31, 2022. Phase 3 randomized controlled trials (RCTs) testing TKIs, including sorafenib and lenvatinib, or ICIs reporting overall survival (OS) and progression-free survival (PFS) were included. Individual survival data were extracted from OS and PFS curves to calculate restricted mean survival time. A Bayesian NMA was performed to compare treatments in terms of efficacy (15- and 30-month OS, 6-month PFS) and safety, represented by grade ≥3 (severe) adverse events (SAEs). The incremental safety-effectiveness ratio as measure of net health benefit was calculated as the difference in SAE probability divided by survival difference between the 2 most effective treatments. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Nine RCTs enrolling 6,600 patients were included. Atezolizumab plus bevacizumab showed the highest probability (88%) of achieving the 30-month OS landmark. Lenvatinib showed a probability of 86% of achieving best PFS outcomes. ICI monotherapies ranked as most tolerable. Atezolizumab plus bevacizumab showed the best net health benefit for OS, compared to durvalumab plus tremelimumab. When evaluating the net health benefit for PFS, at a willingness-to-risk threshold of 10% of SAEs for life-month gained, atezolizumab plus bevacizumab was favoured in 78% of cases, while at threshold of 30% of SAEs for life-month gained, lenvatinib was favoured in 76% of cases. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Atezolizumab plus bevacizumab is the best treatment in terms of net benefit and therefore it should be recommended as standard of care. Compared to atezolizumab plus bevacizumab, lenvatinib monotherapy had the best net benefit for PFS when physicians and patients are available to accept a higher risk of toxicity.
Proton Beam Therapy for Intrahepatic Cholangiocarcinoma: A Multicenter Prospective Registry Study in Japan
Authors: Masashi Mizumoto, Kazuki Terashima, Hirokazu Makishima, Motohisa Suzuki, Takashi Ogino, Takahiro Waki, Hiromitsu Iwata, Hiroyasu Tamamura, Yusuke Uchinami, Tetsuo Akimoto, Tomoaki Okimoto, Takashi Iizumi, Masao Murakami, Norio Katoh, Kazushi Maruo, Kei Shibuya, Hideyuki Sakurai
Journal: Liver Cancer (2023)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Intrahepatic cholangiocarcinoma (ICC) can be treated with chemotherapy in unresectable cases, but outcomes are poor. Proton beam therapy (PBT) may provide an alternative treatment and has good dose concentration that may improve local control. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Fifty-nine patients who received initial PBT for ICC from May 2016 to June 2018 at nine centers were included in the study. The treatment protocol was based on the policy of the Japanese Society for Radiation Oncology. Forty patients received 72.6–76 Gy (RBE) in 20–22 fr, 13 received 74.0–76.0 Gy (RBE) in 37–38 fr, and 6 received 60–70.2 Gy (RBE) in 20–30 fr. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The 59 patients (35 men, 24 women; median age: 71 years; range: 41–91 years) had PS of 0 (&lt;i&gt;n&lt;/i&gt; = 47), 1 (&lt;i&gt;n&lt;/i&gt; = 10), and 2 (&lt;i&gt;n&lt;/i&gt; = 2). Nine patients had hepatitis and all 59 cases were considered inoperable. The Child-Pugh class was A (&lt;i&gt;n&lt;/i&gt; = 46), B (&lt;i&gt;n&lt;/i&gt; = 7), and unknown (&lt;i&gt;n&lt;/i&gt; = 6); the median maximum tumor diameter was 5.0 cm (range 2.0–15.2 cm); and the clinical stage was I (&lt;i&gt;n&lt;/i&gt; = 12), II (&lt;i&gt;n&lt;/i&gt; = 19), III (&lt;i&gt;n&lt;/i&gt; = 10), and IV (&lt;i&gt;n&lt;/i&gt; = 18). At the last follow-up, 17 patients were alive (median follow-up: 36.7 months; range: 24.1–49.9 months) and 42 had died. The median OS was 21.7 months (95% CI: 14.8–34.4 months). At the last follow-up, 37 cases had recurrence, including 10 with local recurrence. The median PFS was 7.5 months (95% CI: 6.1–11.3 months). In multivariable analyses, Child-Pugh class was significantly associated with OS and PFS, and Child-Pugh class and hepatitis were significantly associated with local recurrence. Four patients (6.8%) had late adverse events of grade 3 or higher. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; PBT gives favorable treatment outcomes for unresectable ICC without distant metastasis and may be particularly effective in cases with large tumors.
Incidence of Hyper Progressive Disease in Combination Immunotherapy and Anti-Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Monotherapy for Unresectable Hepatocellular Carcinoma
Authors: Tomoko Aoki, Masatoshi Kudo, Kazuomi Ueshima, Masahiro Morita, Hirokazu Chishina, Masahiro Takita, Satoru Hagiwara, Hiroshi Ida, Yasunori Minami, Masakatsu Tsurusaki, Naoshi Nishida
Journal: Liver Cancer (2023)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling blockade is the most effective strategy for the treatment of immune evading hepatocellular carcinoma (HCC). While immune checkpoint inhibitor has revolutionized the concept of cancer treatment, it has also led to unexpected tumor growth. Regulatory T cells express PD-1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) receptors, which are proliferated and activated by antibody binding, and their ratio to CD8+ T cells is altered, which is one of the causes for hyper progressive disease (HPD). We examined the frequency of HPD in anti-PD-1/PD-L1 monotherapy and combination therapy with vascular endothelial growth factor (VEGF) antibody and anti-CTLA-4 antibodies. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; This was a prospective and retrospective cohort study which enrolled 198 patients with unresectable HCC from January 2015 to December 2021 at the Kindai University Hospital. Fifty-eight patients received anti-PD-1/PD-L1 monotherapy, 119 patients combination with VEGF antibody, and 21 patients combination with anti-CTLA-4 antibody. We defined HPD as tumor growth rate (TGR) ratio ≥4, ΔTGR ≥40%, and tumor growth kinetics ratio ≥4. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The HPD rate was 10.3% (6/58) in anti-PD-1/PD-L1 monotherapy, 1.7% (2/119) in combination with VEGF antibody, and 4.8% (1/21) in combination with anti-CTLA-4 antibody (&lt;i&gt;p&lt;/i&gt; = 0.034). The odds ratio for HPD in the combined anti-CTLA-4 antibody group was 0.433 (95% confidence interval [CI]: 0.05–3.83) when compared to the anti-PD-1/PD-L1 monotherapy group and 2.93 (95% CI: 0.25–33.79) when compared to the combined VEGF antibody group. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; The frequency of HPD in unresectable HCC compared to anti-PD-1/PD-L1 monotherapy was decreased with the combination with anti-VEGF antibody and not increased with anti-CTLA-4 antibody. Anti-PD-1/PD-L1 combined with anti-CTLA-4 antibody is now available in real-world and needs to be further validated with accumulated clinical practice.
Manganese molybdate nanodots with dual amplification of STING activation for “cycle” treatment of metalloimmunotherapy
Authors: Huali Lei, Quguang Li, Guangqiang Li, Tianyi Wang, Xinjing Lv, Zifan Pei, Xiang Gao, Nailin Yang, Fei Gong, Yuqi Yang, Guanghui Hou, Minjiang Chen, Jiansong Ji, Zhuang Liu, Liang Cheng
Journal: Bioactive Materials (2023)

Certain types of cationic metal ions, such as Mn2+ are able to activate immune functions via the stimulator of interferon genes (STING) pathway, showing potential applications in eliciting antitumor immunity. How anionic ions interact with immune cells remains largely unknown. Herein, selecting from a range of cationic and anionic ions, we were excited to discover that MoO42− could act as a cGAS-STING agonist and further confirmed the capability of Mn2+ to activate the cGAS-STING pathway. Inspired by such findings, we synthesized manganese molybdate nanoparticles with polyethylene glycol modification (MMP NDs) for cancer metalloimmunotherapy. Meanwhile, MMP NDs could consume glutathione (GSH) over-expressed in tumors and induce ferroptosis owing to high-valence Mo and Mn to elicit tumor-specific immune responses, which was further amplified by MMP-triggered the cGAS-STING activation. In turn, activated CD8+ T cells to secrete high levels of interferon γ (IFN-γ) and reduced GPX4 expression in tumor cells to trigger ferroptosis-specific lipid peroxidation, which constituted a "cycle" of therapy. As a result, the metalloimmunotherapy with systemic administration of MMP NDs offered a remarkable tumor inhibition effect for a variety of tumor models. Our work for the first time discovered the ability of anionic metal ions to activate the immune system and rationally designed bimetallic oxide nanostructures as a multifunctional therapeutic nanoplatform for tumor immunotherapy.
Bilayer vascular grafts with on-demand NO and H2S release capabilities
Authors: Pengfei Li, Fubang Liang, Lijuan Wang, Dawei Jin, Yushuang Shang, Xu Liu, Yanjun Pan, Jiang Yuan, Jian Shen, Meng Yin
Journal: Bioactive Materials (2023)

Nitric oxide (NO) and hydrogen sulfide (H2S) gasotransmitters exhibit potential therapeutic effects in the cardiovascular system. Herein, biomimicking multilayer structures of biological blood vessels, bilayer small-diameter vascular grafts (SDVGs) with on-demand NO and H2S release capabilities, were designed and fabricated. The keratin-based H2S donor (KTC) with good biocompatibility and high stability was first synthesized and then electrospun with poly (l-lactide-co-caprolactone) (PLCL) to be used as the outer layer of grafts. The electrospun poly (ε-caprolactone) (PCL) mats were aminolyzed and further chelated with copper (II) ions to construct glutathione peroxidase (GPx)-like structural surfaces for the catalytic generation of NO, which acted as the inner layer of grafts. The on-demand release of NO and H2S selectively and synergistically promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs) while inhibiting the proliferation and migration of human umbilical artery smooth muscle cells (HUASMCs). Dual releases of NO and H2S gasotransmitters could enhance their respective production, resulting in enhanced promotion of HUVECs and inhibition of HUASMCs owing to their combined actions. In addition, the bilayer grafts were conducive to forming endothelial cell layers under ﬂow shear stress. In rat abdominal aorta replacement models, the grafts remained patency for 6 months. These grafts were capable of facilitating rapid endothelialization and alleviating neointimal hyperplasia without obvious injury, inflammation, or thrombosis. More importantly, the grafts were expected to avoid calcification with the degradation of the grafts. Taken together, these bilayer grafts will be greatly promising candidates for SDVGs with rapid endothelialization and anti-calcification properties.
A method for assessing rater reliability in applying the Vitiligo Area Scoring Index
Authors: Nishant Kumar, Aunna Pourang, Nneamaka Ezekwe, Angela Parks-Miller, Tasneem F Mohammad, Richard H Huggins, Linda S Deal, Tatjana Lukic, Fan Zhang, Henry W Lim, Iltefat Hamzavi, Indermeet Kohli
Journal: British Journal of Dermatology (2023)

The Vitiligo Area Scoring Index (VASI) is a tool for measuring repigmentation after patients undergo vitiligo treatment, offering a standardized, quantitative scale without the need for specialized equipment. For large multicentre trials that require multiple raters, VASI must be consistently applied to generate interpretable data; therefore, a method for assessing rater reliability would improve data integrity for large clinical studies of vitiligo. This study aimed to assess a method for determining the reliability of VASI raters by evaluating raters of different levels of experience relative to a gold standard.
How Would You Manage This Patient With <i>Clostridioides difficile</i> Infection?
Authors: Zahir Kanjee, Jessica R. Allegretti, Carolyn D. Alonso, Risa B. Burns
Journal: Annals of Internal Medicine (2023)

The Infectious Diseases Society of America/Society for Healthcare Epidemiology of America and the American College of Gastroenterology recently released updated guidelines on management of patients with Clostridioides difficile infection. Although these 2 guidelines generally agree, there are a few important differences in their advice to clinicians. In these rounds, 2 experts, an infectious diseases specialist and a gastroenterologist, discuss antibiotic treatment options for nonsevere disease, the role of fecal microbiota transplantation for fulminant disease, and the use of bezlotoxumab to prevent recurrence in the context of Ms. C, a 48-year-old woman with fulminant C difficile infection.